The Comprehensive Sickle Cell Center of Manhattan is a consortium of 2 medical schools (Columbia and Mt. Sinai) and 4 hospitals (Presbyterian, St. Luke's-Roosevelt, Harlem and Mt. Sinai). The population of patients served consists of 900 individuals, nearly all the patients in the island of Manhattan with sickle cell diseases. The clinical units of the Center provide "state-of-the art" personalized clinical care to the patients, who, in turn, participate in a variety of research projects. One main goal of research activities of the Center focuses on the molecular biology approach to the disease The gene transfer goal is pursued in animals and in vitro, with the control of hemoglobin switching and the creation of transgenic mice as an animal model of the disease as parallel approaches. The patients are genetically classified in detail by DNA analysis and their genotype correlated with clinical manifestation and hematological data to derive prognostic factors that could be used to target therapy. Another area of the Center focuses on therapy: the use of intermittent butyrate therapy offers the promise of increasing Hgb F (it has been shown by another unit of the Center that a HgbF percentage as low as >4% is protective against stroke). Another therapeutic approach is the trial of oral Fe chelator for the patients on chronic transfusion. Studies of neuropsychological damage are correlated with humoral studies of coagulation and of molecules reflecting endothelial damage and integrated with "in vivo" studies of microcirculation. The Center aims to provide cohesion and synergy to all project. The center is assisted by an administrative and statistical core, my a molecular biology and hematological laboratory core, and by an erythropoiesis laboratory core.